Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3 was written by Disch, Jeremy S.;Evindar, Ghotas;Chiu, Cynthia H.;Blum, Charles A.;Dai, Han;Jin, Lei;Schuman, Eli;Lind, Kenneth E.;Belyanskaya, Svetlana L.;Deng, Jianghe;Coppo, Frank;Aquilani, Leah;Graybill, Todd L.;Cuozzo, John W.;Lavu, Siva;Mao, Cheney;Vlasuk, George P.;Perni, Robert B.. And the article was included in Journal of Medicinal Chemistry in 2013.Product Details of 175137-21-0 This article mentions the following:
The sirtuins SIRT1, SIRT2, and SIRT3 are NAD+ dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncol., and neurodegenerative disorders. Encoded library technol. (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA encoded small mols., which identified pan-inhibitors of SIRT1/2/3 with nanomolar potency. Subsequent SAR studies to improve physiochem. properties identified the potent drug like analogs 4-(4-(2-Pivalamidoethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide and 4-(4-(2-(Methylsulfonamido)ethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide. Crystallog. studies of N2-(2-(1-(6-Carbamoylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-yl)ethyl)-N5-ethylthiophene-2,5-dicarboxamide, 4-(4-(2-Pivalamidoethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide, and 4-(4-(2-(Methylsulfonamido)ethyl)piperidin-1-yl)thieno[3,2-d]pyrimidine-6-carboxamide bound in the SIRT3 active site revealed that the common carboxamide binds in the nicotinamide C-pocket and the aliphatic portions of the inhibitors extend through the substrate channel, explaining the observable SAR. These pan SIRT1/2/3 inhibitors, representing a novel chemotype, are significantly more potent than currently available inhibitors, which makes them valuable tools for sirtuin research. In the experiment, the researchers used many compounds, for example, 4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0Product Details of 175137-21-0).
4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. Pyrimidine derivatives have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.Product Details of 175137-21-0
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia